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Covid Pathophysiology and clinical features
1. PATHOPHYSIOLOGY OF COVID 2019
Dr A P Naveen Kumar
Chief Specialist – Gen. Med.
Visakha Steel General Hospital
2.
3. INTRODUCTION
Coronaviruses are enveloped, positive-sense,
single-stranded RNA viruses of ~30 kb
They are largely divided into four genera; α, β, γ,
and δ based on their genomic structure. α and β
coronaviruses infect only mammals
Human coronaviruses such as 229E and NL63
are responsible for common cold and croup and
belong to α coronavirus
In contrast, SARS-CoV, Middle East respiratory
syndrome coronavirus (MERS-CoV) and SARS-
4. Route of entry
Transmission is believed to occur via respiratory
droplets from coughing and sneezing, as with other
respiratory pathogens
Virus released in respiratory secretions can infect
other individuals via direct contact with mucous
membranes
Droplets usually cannot travel more than 6 feet
5. TRANSMISSION
detectable for up to 72 hours on some surfaces despite
decreasing infectivity over time.
very susceptible to high heat (70°C)
At room temperature and moderate (65%) humidity, no
infectious virus could be recovered from printing and
tissue papers after a 3-hour incubation period or from
wood and cloth by day two
On treated smooth surfaces, infectious virus became
undetectable from glass by day 4 and from stainless steel
and plastic by day 7
detectable level of infectious virus could still be
present on the outer layer of a surgical mask on day 7
6. incubationperiod
The median incubation period is 5.1 days
(range 2–14 days)
The precise interval is uncertain.
The period of infectivity starts 2 days prior to
onset of symptoms and lasts up to 8 days
7. The life cycle of the virus with the host consists of
the following 5 steps:
Attachment
Penetration
Biosynthesis
Maturation
Release
Once viruses bind to host receptors (attachment),
they enter host cells through endocytosis or
membrane fusion (penetration).
8.
9. Coronaviruses consist of four structural proteins
Spike (S)
Membrane (M)
Envelope (E)
Nucleocapsid (N)
Spike comprises two functional subunits; S1
subunit is responsible for binding to the host cell
receptor and S2 subunit is for the fusion of the
viral and cellular membranes
10.
11. ACE2 Receptor
The RBD of the S protein of SARS-CoV-2
specifically recognizes the host angiotensin-
converting enzyme 2 (ACE2) receptor
ACE2 receptor -type 2 alveolar epithelial cells in
the lungs, heart, kidney, and gastrointestinal
tract
Lungs seem to be particularly vulnerable
Large surface area
Reservoir for virus replication
12. RAAS- ACE -COVID
ACE2 is a key counterregulatory enzyme that degrades
angiotensin II to angiotensin-(1–7), thereby attenuating its
effects on vasoconstriction, sodium retention, and fibrosis
Despite substantial structural homology between ACE and ACE2,
their enzyme active sites are distinct
ACE inhibitors in clinical use do not directly affect ACE2 activity
SARS-CoV-2 appears to subsequently downregulate ACE2
expression
Unabated angiotensin II activity may be in part responsible for organ
injury in Covid-19
13.
14.
15. Cytokine storm Syndrome -CSS
CSS is an accentuated immune response to
triggers such as viral infections
It results from an excess -proinflammatory and
inadequate anti-inflammatory stimuli
Proinflammatory stimuli - interleukin (IL)–1β, IL-
2, IL-6, IL-7, IL-12, IL-18, tumor necrosis factor
(TNF)–α, interferon (IFN)–γ, and granulocyte
colony-stimulating factor (GCSF)
Anti-inflammatory stimuli include regulatory T
cells, cytokines such as IL-10, transforming
16.
17.
18. CSS
Increased production of IFNγ by hematopoietic
stem cells in response to viral infections is
thought to trigger CSS
CSS - unremitting fever and MODS including
ARDS and acute cardiac and renal injury
Laboratory abnormalities include cytopenias,
increased ferritin, D-dimer, and increased
serum levels of proinflammatory cytokines
Significant increased mortality in patients with
elevated ferritin (>1200 ng/mL) and elevated IL-
19. COVID 2019- Children
Pediatric COVID-19 patients have relatively milder
symptoms in general compared to elder patients
1. the expression level of ACE2 may differ between
adults and children- expressed on well-
differentiated ciliated epithelial cells
2. children have a qualitatively different response to the
SARS-CoV-2 virus to adults
3. presence of other viruses in the mucosa lungs and
airways, common in young children, can let SARS-
CoV-2 virus compete with them and limit its growth
20. COVID -Heart
A large Chinese study analyzed 72 314 patient
records which consisted of 44 672 (61.8%) confirmed
cases, 16 186 (22.4%) suspected cases, and 889
(1.2%) asymptomatic cases.4 Among confirmed
cases in this study, 12.8% had hypertension, 5.3%
diabetes and 4.2% CVD
infection-induced myocarditis and ischaemia.
21.
22. COVID -Heart
CVD - secondary to acute lung injury, which leads to
increased cardiac workload, potentially problematic in
patients with pre existing HF
CSS - result in plaque instability
infiltration of the myocardium by interstitial mononuclear
inflammatory cells
Aside from arterial and venous thrombotic complications
presenting as acute coronary syndromes (ACS) and venous
thromboembolism (VTE), myocarditis plays an important role in
patients with acute heart failure (HF)
Wide range of arrhythmias
23.
24. Bonnie Ky, and Douglas L. Mann J Am Coll Cardiol Basic
Trans Science 2020;5:501-517
2020 The Authors
27. People with COVID-19 have had a wide range of
symptoms reported – ranging from mild symptoms to
severe illness. Symptoms - appear 2-14 days after
exposure
Fever or chills
Cough
Shortness of breath or difficulty breathing
Fatigue
Muscle or body aches
Headache
New loss of taste or smell
Sore throat
Congestion or runny nose
Nausea or vomiting
28. Emergency warning signs* for
COVID-19
Trouble breathing
Persistent pain or pressure in the chest
New confusion
Inability to wake or stay awake
Bluish lips or face
29. HIGH RISK GROUP
Adults 60 years and older
Children younger than 2 years old
Pregnant women and women up to 2 weeks
after the end of pregnancy
People who live in nursing homes and other
long-term care facilities
30. Health and age factors - risk of getting
serious complications
COPD ,Moderate to severe Asthma
CHF ,CAD ,Cardiomyopathies
T2DM
CKD CLD
Obese and BMI > 30
Sickle cell disease
Cancer
Immunocompromised
Pregnancy
CVA
31. SUSPECT CASE
A. A patient with acute respiratory illness (fever and at least
one sign/symptom of respiratory disease, e.g., cough,
shortness of breath), AND a history of travel to or residence in
a location reporting community transmission of COVID-19
disease during the 14 days prior to symptom onset;
OR
B. A patient with any acute respiratory illness AND having been
in contact with a confirmed or probable COVID-19 case in the
last 14 days prior to symptom onset;
OR
C. A patient with severe acute respiratory illness (fever and at
least one sign/symptom of respiratory disease, e.g., cough,
shortness of breath; AND requiring hospitalization) AND in the
absence of an alternative diagnosis that fully explains the
clinical presentation
32. PROBABLE CASE
A. A suspect case for whom testing for the
COVID-19 virus is inconclusive.
OR
B. A suspect case for whom testing could not
be performed for any reason.
33. CONFIRMED CASE
A person with laboratory confirmation of
COVID-19 infection, irrespective of clinical
signs and symptoms
34. As per data from Integrated Health Information
Platform (IHIP)/ Integrated Disease Surveillance
Programme (IDSP) portal case investigation forms
for COVID 19 (n=15,366) 11-6-20
fever (27%)
cough (21%)
sore throat (10%)
breathlessness (8%)
Weakness (7%)
running nose (3%)
and others 24%.
35. Reported symptoms were as follows -USA
Fever (43.1%)
Cough (50.3%)
Shortness of breath (28.5%)
Myalgia (36.1%)
Runny nose (6.1%)
Sore throat (20%)
Headache (34.4%)
Nausea/vomiting (11.5%)
Abdominal pain (7.6%)
Diarrhea (19.3%)
Loss of smell or taste (8.3%)
36. Clinical Severity -MILD
Clinical presentation
Patients with uncomplicated upper respiratory tract
infection, may have mild symptoms such as fever,
cough, sore throat, nasal congestion, malaise,
headache
Clinical parameters
Without evidence of breathlessness or Hypoxia (normal
saturation).
Remarks
Managed at Covid Care Centre
37. Clinical Severity -MODERATE
Clinical presentation
Pneumonia with no signs of severe disease
Clinical parameters
Adolescent or adult - of dyspnea and or hypoxia, fever,
cough, including SpO2
<94% (range 90-94%) on room air, Respiratory Rate more or
equal to 24 per minute.
Child with respiratory distress
Fast breathing (in breaths/min):
< 2 months: ≥ 60
2–11 months: ≥ 50;
1–5 years: ≥ 40
Remarks
Managed in Dedicated Covid Health Centre (DCHC)
38. Clinical Severity -SEVERE
Clinical presentation
Severe Pneumonia
Clinical parameters
Adolescent or adult: with clinical signs of Pneumonia
plus one of the following; respiratory rate >30
breaths/min, severe respiratory distress, SpO2 <90%
on room air.
The diagnosis is clinical; chest imaging can exclude
complications
Remarks
Managed in Dedicated Covid Hospital
39. CHILD
Child with cough or difficulty in breathing, plus
at least one of the following: central cyanosis or
SpO2
<90%; severe respiratory distress (e.g. grunting,
chest in- drawing); signs of pneumonia with any
of the following danger signs: inability to
breastfeed or drink, lethargy or unconsciousness,
or convulsions. Other signs of pneumonia may be
present: chest in drawing, fast breathing (in
breaths/min): <2 months ≥60
2–11 months ≥50
1–5 years ≥40
40. ARDS
Onset: new or worsening respiratory symptoms within one week of known clinical
insult.
Chest imaging (Chest X ray and portable bed side lung ultrasound): bilateral
opacities, not fully explained by effusions, lobar or lung collapse, or nodules.
Origin of Pulmonary infiltrates: respiratory failure not fully explained by cardiac
failure or fluid overload. Need objective assessment (e.g.
echocardiography) to exclude hydrostatic cause of infiltrates/ oedema if no risk
factor present.
Oxygenation impairment in adults:
Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg (with PEEP or CPAP ≥5 cm
H2O)
Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤200 mmHg with PEEP
≥5 cm H2O)
Severe ARDS: PaO2/FiO2 ≤ 100 mmHg with PEEP ≥5 cm H2O)
When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS (including in non-
ventilated patients)
Oxygenation impairment in Children
Note Oxygenation Index (OI) and OSI (Oxygen Saturation Index)
41. SEPSIS
Acute life-threatening organ dysfunction caused
by a dys-regulated host response to suspected
or proven infection.
Signs of organ dysfunction include: altered
mental status, difficult or fast breathing, low
oxygen saturation, reduced urine output, fast
heart rate, weak pulse, cold extremities or low
blood pressure, skin mottling, or laboratory
evidence of coagulopathy, thrombocytopenia,
acidosis, high lactate or hyperbilirubinemia
The Replication Strategy of SARS-CoV (a) The severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) glycoprotein attaches to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. On entering the cytoplasm, the viral core particle, which contains the positive (5′ to 3′) strand genomic ribonucleic acid (RNA), is released into the cytoplasm of the cell (b). The positive-strand viral RNA is translated on host ribosomes to generate a large polyprotein (c) that undergoes proteolytic processing to generate multiple viral proteins, including an RNA-dependent RNA polymerase (RdRp). The RNA-dependent RNA polymerase generates a full-length, antisense negative-strand (3′ to 5′) viral RNA strand (d) that serves as template for replicating positive-strand viral genomic RNA, as well as shorter negative-strand RNAs (e) that serve as templates for synthesizing messenger ribonucleic acids (mRNAs) that code for structural proteins of the virus (f), including the S, membrane (M), envelope (E), and nucleocapsid (N) proteins. Translation of viral mRNAs occurs using the host endoplasmic reticulum (ER) (g). Once the viral structural proteins, S, E, and M, are translated and inserted into the ER, they move along the secretory pathway to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (h). The viral proteins become encapsulated and bud into membranes containing viral structural proteins, where mature virions are assembled. (i) Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis. Modified from Turner et al. (43). ORF = open reading frame.